ExonSkipDB: functional annotation of exon skipping event in human

Gene summary for ME2

Gene summary

Gene information	Gene symbol	ME2
	Gene ID	4200
	Gene name	malic enzyme 2
	Synonyms	ODS1
	Cytomap	18q21.2
	Type of gene	protein-coding
	Description	NAD-dependent malic enzyme, mitochondrialNAD-MEmalate dehydrogenase (oxaloacetate-decarboxylating)malic enzyme 2, NAD(+)-dependent, mitochondrialpyruvic-malic carboxylase
	Modification date	20180523
	UniProtAcc	P23368
	Context	PubMed: ME2 [Title/Abstract] AND exon [Title/Abstract] AND skip [Title/Abstract] - Title (PMID)

Gene ontology of each this gene with evidence of Inferred from Direct Assay (IDA) from Entrez

Gene

GO ID

GO term

PubMed ID

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Exon skipping events across known transcript of Ensembl for ME2 from UCSC genome browser

Skipped exons in TCGA and GTEx based on Ensembl gene isoform structure.
* Click on the image to open the UCSC genome browser with custom track showing this image in a new window.

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Gene isoform structures and expression levels for ME2

Expression levels of gene isoforms across TCGA.

Expression levels of gene isoforms across GTEx.

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Exon skipping events with PSIs in TCGA for ME2

Information of exkip skipping event in TCGA.

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon	ENSG	ENSTs
exon_skip_296861	18	48405489:48405678:48422178:48422298:48434432:48434566	48422178:48422298	ENSG00000082212.7	ENST00000382927.3
exon_skip_296862	18	48434432:48434566:48439170:48439320:48442537:48442613	48439170:48439320	ENSG00000082212.7	ENST00000382927.3,ENST00000321341.5
exon_skip_296865	18	48439170:48439320:48442537:48442613:48443716:48443878	48442537:48442613	ENSG00000082212.7	ENST00000382927.3,ENST00000321341.5
exon_skip_296870	18	48442537:48442613:48443716:48443878:48444479:48444583	48443716:48443878	ENSG00000082212.7	ENST00000382927.3,ENST00000321341.5
exon_skip_296872	18	48447030:48447128:48447443:48447557:48450467:48450582	48447443:48447557	ENSG00000082212.7	ENST00000382927.3,ENST00000321341.5
exon_skip_296873	18	48447443:48447557:48450467:48450582:48452125:48452268	48450467:48450582	ENSG00000082212.7	ENST00000382927.3,ENST00000321341.5
exon_skip_296875	18	48452229:48452268:48458627:48458730:48466657:48466756	48458627:48458730	ENSG00000082212.7	ENST00000585680.1
exon_skip_296876	18	48458627:48458730:48465939:48466010:48466657:48466756	48465939:48466010	ENSG00000082212.7	ENST00000321341.5
exon_skip_296878	18	48458627:48458730:48466657:48466756:48473386:48473524	48466657:48466756	ENSG00000082212.7	ENST00000585680.1

PSI values of skipped exons in TCGA.

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Exon skipping events with PSIs in GTEx for ME2

Information of exkip skipping event in GTEx

Exon skip ID	chr	Exons involved in exon skipping	Skipped exon	ENSG	ENSTs
exon_skip_296861	18	48405489:48405678:48422178:48422298:48434432:48434566	48422178:48422298	ENSG00000082212.7	ENST00000382927.3
exon_skip_296862	18	48434432:48434566:48439170:48439320:48442537:48442613	48439170:48439320	ENSG00000082212.7	ENST00000321341.5,ENST00000382927.3
exon_skip_296865	18	48439170:48439320:48442537:48442613:48443716:48443878	48442537:48442613	ENSG00000082212.7	ENST00000321341.5,ENST00000382927.3
exon_skip_296870	18	48442537:48442613:48443716:48443878:48444479:48444583	48443716:48443878	ENSG00000082212.7	ENST00000321341.5,ENST00000382927.3
exon_skip_296872	18	48447030:48447128:48447443:48447557:48450467:48450582	48447443:48447557	ENSG00000082212.7	ENST00000321341.5,ENST00000382927.3
exon_skip_296873	18	48447443:48447557:48450467:48450582:48452125:48452268	48450467:48450582	ENSG00000082212.7	ENST00000321341.5,ENST00000382927.3
exon_skip_296875	18	48452229:48452268:48458627:48458730:48466657:48466756	48458627:48458730	ENSG00000082212.7	ENST00000585680.1
exon_skip_296876	18	48458627:48458730:48465939:48466010:48466657:48466756	48465939:48466010	ENSG00000082212.7	ENST00000321341.5
exon_skip_296878	18	48458627:48458730:48466657:48466756:48473386:48473524	48466657:48466756	ENSG00000082212.7	ENST00000585680.1

PSI values of skipped exons in GTEx.

* Skipped exon sequences.

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Open reading frame (ORF) annotation in the exon skipping event for ME2

Open reading frame (ORF) of individual exon skipping events in TCGA based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000321341	48442537	48442613	Frame-shift
ENST00000321341	48450467	48450582	Frame-shift
ENST00000321341	48465939	48466010	Frame-shift
ENST00000321341	48439170	48439320	In-frame
ENST00000321341	48443716	48443878	In-frame
ENST00000321341	48447443	48447557	In-frame

Open reading frame (ORF) of individual exon skipping events in GTEx based on the Ensembl gene structure combined from isoforms.

ENST	Start of skipped exon	End of skipped exon	ORF
ENST00000321341	48442537	48442613	Frame-shift
ENST00000321341	48450467	48450582	Frame-shift
ENST00000321341	48465939	48466010	Frame-shift
ENST00000321341	48439170	48439320	In-frame
ENST00000321341	48443716	48443878	In-frame
ENST00000321341	48447443	48447557	In-frame

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Infer the effects of exon skipping event on protein functional features for ME2

Exon skipping at the protein sequence level and followed lost functional features.
* Click on the image to enlarge it in a new window.

Loci of skipped exons in TCGA across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000321341	3181	584	48439170	48439320	515	664	81	130
ENST00000321341	3181	584	48443716	48443878	741	902	156	210
ENST00000321341	3181	584	48447443	48447557	1215	1328	314	352

Loci of skipped exons in GTEx across genomic, transcript, and protein sequence levels of In-frame cases.

ENST	Length of mRNA	Length of AA seq.	Genomic start	Genomic end	mRNA start	mRNA end	AA start	AA end
ENST00000321341	3181	584	48439170	48439320	515	664	81	130
ENST00000321341	3181	584	48443716	48443878	741	902	156	210
ENST00000321341	3181	584	48447443	48447557	1215	1328	314	352

Lost protein functional features of individual exon skipping events in TCGA.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
P23368	81	130	112	112	Active site	Note=Proton donor
P23368	81	130	91	91	Binding site	Note=Allosteric activator;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12121650,ECO:0000269\|PubMed:12962632;Dbxref=PMID:12121650,PMID:12962632
P23368	81	130	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	81	130	78	89	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	93	102	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	104	111	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	115	121	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	123	126	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	91	91	Mutagenesis	Note=Abolishes activation by fumarate. R->T;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12121650;Dbxref=PMID:12121650
P23368	81	130	114	114	Natural variant	ID=VAR_034104;Note=P->L;Dbxref=dbSNP:rs16952692
P23368	156	210	183	183	Active site	Note=Proton acceptor
P23368	156	210	157	161	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	163	165	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	198	205	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	165	165	Binding site	Note=Substrate;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12962632;Dbxref=PMID:12962632
P23368	156	210	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	156	210	173	177	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	178	191	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	195	197	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	156	156	Modified residue	Note=N6-acetyllysine;Ontology_term=ECO:0000244;evidence=ECO:0000244\|PubMed:19608861;Dbxref=PMID:19608861
P23368	156	210	165	173	Nucleotide binding	Note=NAD;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10700286,ECO:0000269\|PubMed:12962632;Dbxref=PMID:10700286,PMID:12962632
P23368	156	210	167	169	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1QR6
P23368	314	352	341	345	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	314	352	314	329	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	334	339	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	346	346	Modified residue	Note=N6-acetyllysine;Ontology_term=ECO:0000244;evidence=ECO:0000244\|PubMed:19608861;Dbxref=PMID:19608861
P23368	314	352	311	328	Nucleotide binding	Note=NAD;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10700286,ECO:0000269\|PubMed:12962632;Dbxref=PMID:10700286,PMID:12962632

Lost protein functional features of individual exon skipping events in GTEx.

UniProt acc.	Start of exon skipping (AA)	End of exon skipping (AA)	Protein feature start (AA)	Protein feature end (AA)	Category of protein feature	Description of feature
P23368	81	130	112	112	Active site	Note=Proton donor
P23368	81	130	91	91	Binding site	Note=Allosteric activator;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:12121650,ECO:0000269\|PubMed:12962632;Dbxref=PMID:12121650,PMID:12962632
P23368	81	130	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	81	130	78	89	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	93	102	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	104	111	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	115	121	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	123	126	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	81	130	91	91	Mutagenesis	Note=Abolishes activation by fumarate. R->T;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12121650;Dbxref=PMID:12121650
P23368	81	130	114	114	Natural variant	ID=VAR_034104;Note=P->L;Dbxref=dbSNP:rs16952692
P23368	156	210	183	183	Active site	Note=Proton acceptor
P23368	156	210	157	161	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	163	165	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	198	205	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	165	165	Binding site	Note=Substrate;Ontology_term=ECO:0000269;evidence=ECO:0000269\|PubMed:12962632;Dbxref=PMID:12962632
P23368	156	210	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	156	210	173	177	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	178	191	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	195	197	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	156	210	156	156	Modified residue	Note=N6-acetyllysine;Ontology_term=ECO:0000244;evidence=ECO:0000244\|PubMed:19608861;Dbxref=PMID:19608861
P23368	156	210	165	173	Nucleotide binding	Note=NAD;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10700286,ECO:0000269\|PubMed:12962632;Dbxref=PMID:10700286,PMID:12962632
P23368	156	210	167	169	Turn	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1QR6
P23368	314	352	341	345	Beta strand	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	19	584	Chain	ID=PRO_0000018537;Note=NAD-dependent malic enzyme%2C mitochondrial
P23368	314	352	314	329	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	334	339	Helix	Ontology_term=ECO:0000244;evidence=ECO:0000244\|PDB:1PJ3
P23368	314	352	346	346	Modified residue	Note=N6-acetyllysine;Ontology_term=ECO:0000244;evidence=ECO:0000244\|PubMed:19608861;Dbxref=PMID:19608861
P23368	314	352	311	328	Nucleotide binding	Note=NAD;Ontology_term=ECO:0000269,ECO:0000269;evidence=ECO:0000269\|PubMed:10700286,ECO:0000269\|PubMed:12962632;Dbxref=PMID:10700286,PMID:12962632

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SNVs in the skipped exons for ME2

- Lollipop plot for presenting exon skipping associated SNVs.
* Click on the image to enlarge it in a new window.

- Differential PSIs between mutated versus non-mutated samples.

ME2_HNSC_exon_skip_296872_psi_boxplot.png
boxplot

- Non-synonymous mutations located in the skipped exons in TCGA.

Cancer type	Sample	ESID	Skipped exon start	Skipped exon end	Mutation start	Mutation end	Mutation type	Reference seq	Mutation seq	AAchange
SKCM	TCGA-RP-A6K9-06	exon_skip_296861	48422179	48422298	48422258	48422258	Frame_Shift_Del	A	-	p.E23fs
LIHC	TCGA-DD-A1EG-01	exon_skip_296870	48443717	48443878	48443764	48443764	Frame_Shift_Del	G	-	p.L172fs
LIHC	TCGA-DD-A3A0-01	exon_skip_296870	48443717	48443878	48443863	48443863	Frame_Shift_Del	G	-	p.V205fs
BLCA	TCGA-CU-A0YR-01	exon_skip_296873	48450468	48450582	48450474	48450480	Frame_Shift_Del	AAAGCAA	-	p.K355fs
BLCA	TCGA-CU-A0YR-01	exon_skip_296873	48450468	48450582	48450474	48450480	Frame_Shift_Del	AAAGCAA	-	p.KAK355fs
LIHC	TCGA-BC-A3KG-01	exon_skip_296876	48465940	48466010	48465991	48465991	Frame_Shift_Del	T	-	p.V490fs
LIHC	TCGA-DD-A39Y-01	exon_skip_296878	48466658	48466756	48466692	48466692	Frame_Shift_Del	C	-	p.A508fs
LIHC	TCGA-DD-A1EG-01	exon_skip_296878	48466658	48466756	48466697	48466697	Frame_Shift_Del	G	-	p.G510fs
LUAD	TCGA-17-Z057-01	exon_skip_296878	48466658	48466756	48466751	48466752	Frame_Shift_Ins	-	T	p.*528fs
HNSC	TCGA-CV-A461-01	exon_skip_296872	48447444	48447557	48447542	48447542	Nonsense_Mutation	T	G	p.Y347*
COAD	TCGA-CM-4743-01	exon_skip_296875	48458628	48458730	48458685	48458685	Nonsense_Mutation	C	T	p.R458X
STAD	TCGA-BR-4184-01	exon_skip_296875	48458628	48458730	48458685	48458685	Nonsense_Mutation	C	T	p.R458*

- Depth of coverage in the three exons composing exon skipping event

Depth of coverage in three exons	Mutation description
	Sample: TCGA-CV-A461-01
	Cancer type: HNSC
	ESID: exon_skip_296872
	Skipped exon start: 48447444
	Skipped exon end: 48447557
	Mutation start: 48447542
	Mutation end: 48447542
	Mutation type: Nonsense_Mutation
	Reference seq: T
	Mutation seq: G
	AAchange: p.Y347*
exon_skip_296872_HNSC_TCGA-CV-A461-01.png

- Non-synonymous mutations located in the skipped exons in CCLE.

Sample	Skipped exon start	Skipped exon end	Mutation start	Mutation end	Mutation type	Reference seq	Mutation seq	AAchange
NALM6_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE	48439171	48439320	48439301	48439301	Missense_Mutation	C	T	p.H125Y
SNU1040_LARGE_INTESTINE	48442538	48442613	48442573	48442573	Missense_Mutation	T	C	p.V143A
RPMI8402_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE	48443717	48443878	48443856	48443856	Missense_Mutation	T	C	p.I203T
CHL1_SKIN	48447444	48447557	48447448	48447448	Missense_Mutation	C	G	p.A316G
SW1463_LARGE_INTESTINE	48447444	48447557	48447448	48447448	Missense_Mutation	C	G	p.A316G
ML2_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE	48447444	48447557	48447510	48447510	Missense_Mutation	G	A	p.A337T
JJN3_HAEMATOPOIETIC_AND_LYMPHOID_TISSUE	48450468	48450582	48450471	48450471	Missense_Mutation	C	T	p.R354W
HEC108_ENDOMETRIUM	48458628	48458730	48458695	48458695	Missense_Mutation	C	T	p.T461I
HUH6_LIVER	48466658	48466756	48466686	48466686	Missense_Mutation	A	C	p.E506A
HUH6CLONE5_LIVER	48466658	48466756	48466686	48466686	Missense_Mutation	A	C	p.E506A
SNU81_LARGE_INTESTINE	48422179	48422298	48422297	48422297	Splice_Site	A	C	p.K36T
ISHIKAWAHERAKLIO02ER_ENDOMETRIUM	48466658	48466756	48466755	48466758	Splice_Site	AAGT	-	p.K529fs

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Splicing Quantitative Trait Loci (sQTL) in the exon skipping event for ME2

sQTL information located at the skipped exons.

Exon skip ID

Chromosome

Three exons

Skippped exon

ENST

Cancer type

SNP id

Location

DNA change (ref/var)

P-value

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Splicing Quantitative Trait Methylation (sQTM) in the skipped exon for ME2

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Survival analysis of Splicing Quantitative Trait Methylation (sQTM) in the skipped exon for ME2

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RelatedDrugs for ME2

Approved drugs targeting this gene.
(DrugBank Version 5.1.0 2018-04-02)

Gene

UniProtAcc

DrugBank ID

Drug name

Drug activity

Drug type

Drug status

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RelatedDiseases for ME2

Diseases associated with this gene.
(DisGeNet 4.0)

Gene	Disease ID	Disease name	# pubmeds	Source
ME2	C0005586	Bipolar Disorder	1	PSYGENET
ME2	C0024713	Manic Disorder	1	PSYGENET
ME2	C0033975	Psychotic Disorders	1	PSYGENET
ME2	C0036341	Schizophrenia	1	PSYGENET
ME2	C0338831	Manic	1	PSYGENET
ME2	C0349204	Nonorganic psychosis	1	PSYGENET

	Gene summary
	Gene structures and expression levels
	Exon skipping events with PSIs in TCGA
	Exon skipping events with PSIs in GTEx
	Open reading frame (ORF) annotation in the exon skipping event
	Exon skipping events in the canonical protein sequence
	SNVs in the skipped exons with depth of coverage
	Splicing Quantitative Trait Loci (sQTLs) in the skipped exons
	Splicing Quantitative Trait Methylation (sQTM) in the skipped exon
	Related drugs with this gene
	Related diseases with this gene

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